Systems serology detects functionally distinct coronavirus antibody features in children and elderly

Kevin J. Selva; Carolien E. van de Sandt; Melissa M. Lemke; Christina Y. Lee; Suzanne K. Shoffner; Brendon Y. Chua; Samantha K. Davis; Thi H.O. Nguyen; Louise C. Rowntree; Luca Hensen; Marios Koutsakos; Chinn Yi Wong; Francesca Mordant; David C. Jackson; Katie L. Flanagan; Jane Crowe; Shidan Tosif; Melanie R. Neeland; Philip Sutton; Paul V. Licciardi; Nigel W. Crawford; Allen C. Cheng; Denise L. Doolan; Fatima Amanat; Florian Krammer; Keith Chappell; Naphak Modhiran; Daniel Watterson; Paul Young; Wen Shi Lee; Bruce D. Wines; P. Mark Hogarth; Robyn Esterbauer; Hannah G. Kelly; Hyon Xhi Tan; Jennifer A. Juno; Adam K. Wheatley; Stephen J. Kent; Kelly B. Arnold; Katherine Kedzierska; Amy W. Chung

doi:10.1038/s41467-021-22236-7

Systems serology detects functionally distinct coronavirus antibody features in children and elderly

Kevin J. Selva, Carolien E. van de Sandt, Melissa M. Lemke, Christina Y. Lee, Suzanne K. Shoffner, Brendon Y. Chua, Samantha K. Davis, Thi H.O. Nguyen, Louise C. Rowntree, Luca Hensen, Marios Koutsakos, Chinn Yi Wong, Francesca Mordant, David C. Jackson, Katie L. Flanagan, Jane Crowe, Shidan Tosif, Melanie R. Neeland, Philip Sutton, Paul V. LicciardiNigel W. Crawford, Allen C. Cheng, Denise L. Doolan, Fatima Amanat, Florian Krammer, Keith Chappell, Naphak Modhiran, Daniel Watterson, Paul Young, Wen Shi Lee, Bruce D. Wines, P. Mark Hogarth, Robyn Esterbauer, Hannah G. Kelly, Hyon Xhi Tan, Jennifer A. Juno, Adam K. Wheatley, Stephen J. Kent, Kelly B. Arnold, Katherine Kedzierska, Amy W. Chung

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117 Scopus citations

Abstract

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.

Original language	English
Article number	2037
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-22236-7
State	Published - 1 Dec 2021

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Selva, K. J., van de Sandt, C. E., Lemke, M. M., Lee, C. Y., Shoffner, S. K., Chua, B. Y., Davis, S. K., Nguyen, T. H. O., Rowntree, L. C., Hensen, L., Koutsakos, M., Wong, C. Y., Mordant, F., Jackson, D. C., Flanagan, K. L., Crowe, J., Tosif, S., Neeland, M. R., Sutton, P., ... Chung, A. W. (2021). Systems serology detects functionally distinct coronavirus antibody features in children and elderly. Nature Communications, 12(1), Article 2037. https://doi.org/10.1038/s41467-021-22236-7

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title = "Systems serology detects functionally distinct coronavirus antibody features in children and elderly",

abstract = "The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.",

author = "Selva, {Kevin J.} and {van de Sandt}, {Carolien E.} and Lemke, {Melissa M.} and Lee, {Christina Y.} and Shoffner, {Suzanne K.} and Chua, {Brendon Y.} and Davis, {Samantha K.} and Nguyen, {Thi H.O.} and Rowntree, {Louise C.} and Luca Hensen and Marios Koutsakos and Wong, {Chinn Yi} and Francesca Mordant and Jackson, {David C.} and Flanagan, {Katie L.} and Jane Crowe and Shidan Tosif and Neeland, {Melanie R.} and Philip Sutton and Licciardi, {Paul V.} and Crawford, {Nigel W.} and Cheng, {Allen C.} and Doolan, {Denise L.} and Fatima Amanat and Florian Krammer and Keith Chappell and Naphak Modhiran and Daniel Watterson and Paul Young and Lee, {Wen Shi} and Wines, {Bruce D.} and {Mark Hogarth}, P. and Robyn Esterbauer and Kelly, {Hannah G.} and Tan, {Hyon Xhi} and Juno, {Jennifer A.} and Wheatley, {Adam K.} and Kent, {Stephen J.} and Arnold, {Kelly B.} and Katherine Kedzierska and Chung, {Amy W.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

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doi = "10.1038/s41467-021-22236-7",

language = "English",

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Selva, KJ, van de Sandt, CE, Lemke, MM, Lee, CY, Shoffner, SK, Chua, BY, Davis, SK, Nguyen, THO, Rowntree, LC, Hensen, L, Koutsakos, M, Wong, CY, Mordant, F, Jackson, DC, Flanagan, KL, Crowe, J, Tosif, S, Neeland, MR, Sutton, P, Licciardi, PV, Crawford, NW, Cheng, AC, Doolan, DL, Amanat, F, Krammer, F, Chappell, K, Modhiran, N, Watterson, D, Young, P, Lee, WS, Wines, BD, Mark Hogarth, P, Esterbauer, R, Kelly, HG, Tan, HX, Juno, JA, Wheatley, AK, Kent, SJ, Arnold, KB, Kedzierska, K & Chung, AW 2021, 'Systems serology detects functionally distinct coronavirus antibody features in children and elderly', Nature Communications, vol. 12, no. 1, 2037. https://doi.org/10.1038/s41467-021-22236-7

TY - JOUR

T1 - Systems serology detects functionally distinct coronavirus antibody features in children and elderly

AU - Selva, Kevin J.

AU - van de Sandt, Carolien E.

AU - Lemke, Melissa M.

AU - Lee, Christina Y.

AU - Shoffner, Suzanne K.

AU - Chua, Brendon Y.

AU - Davis, Samantha K.

AU - Nguyen, Thi H.O.

AU - Rowntree, Louise C.

AU - Hensen, Luca

AU - Koutsakos, Marios

AU - Wong, Chinn Yi

AU - Mordant, Francesca

AU - Jackson, David C.

AU - Flanagan, Katie L.

AU - Crowe, Jane

AU - Tosif, Shidan

AU - Neeland, Melanie R.

AU - Sutton, Philip

AU - Licciardi, Paul V.

AU - Crawford, Nigel W.

AU - Cheng, Allen C.

AU - Doolan, Denise L.

AU - Amanat, Fatima

AU - Krammer, Florian

AU - Chappell, Keith

AU - Modhiran, Naphak

AU - Watterson, Daniel

AU - Young, Paul

AU - Lee, Wen Shi

AU - Wines, Bruce D.

AU - Mark Hogarth, P.

AU - Esterbauer, Robyn

AU - Kelly, Hannah G.

AU - Tan, Hyon Xhi

AU - Juno, Jennifer A.

AU - Wheatley, Adam K.

AU - Kent, Stephen J.

AU - Arnold, Kelly B.

AU - Kedzierska, Katherine

AU - Chung, Amy W.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.

AB - The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.

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U2 - 10.1038/s41467-021-22236-7

DO - 10.1038/s41467-021-22236-7

M3 - Article

C2 - 33795692

AN - SCOPUS:85103806412

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2037

ER -

Systems serology detects functionally distinct coronavirus antibody features in children and elderly

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